Microfluidic and nanofluidic (hereinafter collectively referred to as microfluidic) technologies provide promising alternatives for acquiring information from and detecting chemical and biological samples. Biochemical and chemical reactions, processes, separation, identification, and detection, both simple and complex, can be carried out using microfluidic technology. Microfluidic technology provides many benefits over conventional systems. These benefits include, for example, smaller sample sizes, ease of portability, reduced laboratory area requirements, and shorter processing periods. As a consequence of these many benefits, microfluidic technology has attracted interest in a variety of technical disciplines for use in diverse applications. Examples of some applications for which microfluidic technology is particularly suited include chromatographic separations, filtrations, analytical chemistry, chemical and biological synthesis, DNA amplification, and screening of chemical and biological agents for activity. It is envisioned that many of these applications will be carried out on what are known as miniaturized lab-on-chips and microelectromechanical (MEM) systems.
Liquid chromatography is a physical separation technique in which a liquid mobile phase, typically containing a solvent, carries a sample containing multiple constituents or species (e.g., proteins and other biomolecules) along a column or trench containing one more packing materials, which interact with the sample to separate sample constituents or species from one another. In the context of a microfluidic system, the packing materials are deposited in a microfluidic channel having a width and/or depth on the order of tenths of nanometers to a few millimeters. Interaction between the packing materials and liquid mobile phase which effects separation of chemical constituents and biological agents may involve, for example, adsorption, ion exchange, partitioning, and size exclusion.
In some applications it is desirable to fill the entire microfluidic channel with packing material, whereas in other applications it is desirable to fill less than the entire microfluidic channel with the packing material. A partially filled microfluidic channel may take several forms, with each form possessing its own advantages. For example, according to one embodiment, partial filling of the microfluidic channel may create a continuous permeable wall extending along the microfluidic channel, with a coextensive vacant space extending longitudinally between the permeable material and the base surface of the microfluidic channel. The provision of the continuous vacant area above or below the permeable wall may, for example, reduce the pressure requirement for flowing an analyte solution through the microfluidic channel. According to another embodiment, differing packing materials are packed into discrete longitudinal segments of the microfluidic channel, with adjacent packing material segments either contacting one another or being spaced apart from one another lengthwise along the microfluidic channel. The provision of multiple distinct packing material segments along a portion or the entire length of the microfluidic channel permits the fluid sample to interact with multiple different materials, permitting analyses of multiple interactions and, depending upon the particular packing materials selected, enhancing constituent/agent separation of the sample.
One manner of attempting to fill or partially fill a microfluidic channel is to pack micro- or nano-particles into the channel after substrates defining the microfluidic channel have been assembled together. It is believed that this post-assembly packing technique would be problematic because the extremely small dimensions of the channels would make it difficult, if not impossible in some situations, to apply sufficient pressure for forcing the particles into and along the entire length of the channels without rupturing the bond between the substrates. Another envisioned problem of this post-assembly packing technique would relate to the handling of micro-sized packing micro- and nano-particles. It is further believed that this post-assembly packing technique also would not be conducive towards controlling the partial filling of microfluidic channels. Using this technique, it would be difficult to create a permeable wall of uniform wall height or permeable wall discrete section spaced apart from one another longitudinally along the microfluidic channel.
Another technique that could be attempted for packing microfluidic channels is to pack the particles into microfluidic channels of a first substrate, then to assemble a second substrate on the first substrate and thereby enclose the microfluidic channel. It is believed that this fabrication technique would be problematic with regard to its handling of micro-sized packing materials. It is further believed that it would be difficult to create a uniform wall height with uniform spacing from the channel base for creating partially filled microfluidic channels.